LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer

Cancer Med. 2018 Mar;7(3):842-855. doi: 10.1002/cam4.1353. Epub 2018 Feb 23.

Abstract

To study the regulatory effect of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT-PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull-down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR-20a-5p, as well as relationship of miR-20a-5p with high mobility group AT-hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR-20a-5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR-20a-5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR-20a-5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR-20a-5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer.

Keywords: HMGA2; Breast cancer; lncRNA HOTAIR; miR-20a-5p.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Female
  • Heterografts
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Transfection

Substances

  • HOTAIR long untranslated RNA, human
  • MIRN20a microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding